Bimiralisib free base

• CAS: 1225037-39-7
• Catalog Number: ACM1225037397
• Category: Inhibitors
• Molecular Weight: 411.39
• Molecular Formula: C17H20F3N7O2
• Description: Bimiralisib, also known as PQR309, is an orally bioavailable pan inhibitor of phosphoinositide-3-kinases (PI3K) and inhibitor of the mammalian target of rapamycin (mTOR), with potential antineoplastic activity. PI3K/mTOR kinase inhibitor PQR309 inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a lesser extent, mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy.
• Synonyms: PQR309; PQR-309; PQR309; Bimiralisib free base
• IUPAC Name: 5-(4,6-dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine
• Canonical SMILES: NC1=NC=C(C2=NC(N3CCOCC3)=NC(N4CCOCC4)=N2)C(C(F)(F)F)=C1
• InChI: InChI=1S/C17H20F3N7O2/c18-17(19,20)12-9-13(21)22-10-11(12)14-23-15(26-1-5-28-6-2-26)25-16(24-14)27-3-7-29-8-4-27/h9-10H,1-8H2,(H2,21,22)
• InChI Key: ADGGYDAFIHSYFI-UHFFFAOYSA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 1820902-72-4 (HCl salt); 1225037-39-7 (free base)
• Biological Target: Bimiralisib (PQR309) is a brain-penetrant, pan-class I PI3K/mTOR inhibitor with IC50s of 33 nM, 451 nM, 661 nM, 708 nM and 89 nM for PI3Kα, PI3Kδ, PI3Kβ, PI3Kγ and mTOR, respectively.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 49.63; H, 4.90; F, 13.85; N, 23.83; O, 7.78
• Exact Mass: 411.1631
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: The results of a CCK-8 assay revealed a significant suppressive effect of PQR309 on U87 and U251 cells. The results indicated that the viability of the cells was significantly (P<0.05) suppressed in a dose- and time-dependent manner after the cells were treated with PQR309 (0, 1, 5, 10, 50 and 100 µM) after 72 h (Fig. 1B). The colony formation rates of treated U87 and U251 cells decreased in various concentration groups compared to the control (Fig. 1C-D). According to these results, the IC50 values of PQR309 were 7.104 (95% CI, 5.6-8.5) and 11.986 (95% CI, 10.6-13.4) in U87 and U251 cells, respectively.; Reference: Oncol Rep. 2020 Mar; 43(3): 773-782. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040887/
• In Vivo Activity: Rats were injected with 2 × 107 human PC3 prostate cancer cells into one flank and randomized after 16 days. From day 17 the control group received vehicle once daily. Compound 1 (bimiralisib) was orally administered at 5 mg/kg, 10 mg/kg (both daily, QD), or 15 mg/kg [5 consecutive days, 2 days off drug (QD × 5, 2 days off)] for 28 days to match the timelines of regulatory toxicology studies. Treatment with 1 led to significant tumor size reductions: tumor growth was inhibited dose-dependently (best T/C of 31-12%, Figure 6A). Compound 1 was best tolerated at 5 mg/kg without significant body weight changes (Figure 6B). At 10 mg/kg, 1 caused a reduction of body weight, which accumulated to a reduction of 15% after 28 days of treatment. Similarly, 15 mg/kg of 1 led to body weight loss after 5 days of treatment, which was reversible during the recovery period. After 28 days of drug exposure (day 44 of the experiment), animals with body weight loss fully recovered within a treatment-free period (days 45-50) without overt signs of tumor cell proliferation. In a subsequent treatment period tumor growth remained inhibited and body weight loss was only observed in the 15 mg/kg group.; Reference: J Med Chem. 2017 Sep 14; 60(17): 7524-7538. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656176/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).